MOLECULAR BIOLOGY AND MECHANICS OF CARDIAC INTERSTITIUM

心脏间质的分子生物学和力学

• 批准号: 2396245
• 负责人: JAMES W COVELL
• 金额: $ 30.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2396245
• 关键词: collagen; coronary occlusion /thrombosis; disease /disorder model; extracellular matrix; fibroblasts; histogenesis; mechanical stress; myocardial infarction; reperfusion; scars; swine; tissue /cell culture; transforming growth factors; wound healing

DESCRIPTION (adapted from the applicant's abstract): The overall objective of this proposal is to test the hypothesis that scar anisotropy is a desired structural feature that contributes importantly to the normal function of adjacent myocardium. The applicant will examine for the roles that mechanical stretch, preexisting extracellular matrix and the upregulation of Transforming Growth Factor-b1 (TGF-b1) play in defining the anisotropic structure of the myocardial scar. Initial studies are designed to define the normal spatial gradient of finite deformation in myocardium adjacent to the healing scar in a pig model of myocardial infarction. To directly test the hypothesis that the unique structure of the scar influences function in adjacent myocardium the applicant proposes to modify scar structure by manipulating local levels of TGF-b1 during healing. Additional studies to be performed in the pig model of infarction and in vitro in cultured cardiac fibroblasts will test for the roles that mechanical deformations, preexisting matrix and TGF-b1 have on defining scar structure and function. Clinically, it is known that the timely reperfusion of acutely ischemic myocardium can reduce infarct size and preserve left ventricular function. This approach has become the treatment of choice within hours of coronary occlusion. There is evidence that strength and collagen content of reperfused scars differs from that of permanently occluded myocardium. However, beyond these observations little is known about scar structure and function of bordering myocardium in the setting of coronary occlusion and reperfusion. Thus, as a third aim of the proposal the applicant will examine in infarcted-reperfused pig myocardium the structural features and mechanical properties of scar tissue as well as function in bordering myocardium.

描述（改编自申请人的摘要）：总体目标 这个建议的目的是检验疤痕各向异性是一个理想的假设， 对正常功能有重要贡献的结构特征 邻近心肌 申请人将检查的角色， 机械拉伸，预先存在的细胞外基质和上调 转化生长因子-b1（TGF-β 1）在定义各向异性 心肌瘢痕的结构。 初步研究旨在确定 相邻心肌有限变形的正常空间梯度 猪心肌梗死模型中的愈合疤痕。 直接测试 疤痕的独特结构影响功能的假设， 申请人提出通过以下方法来改变瘢痕结构 在愈合过程中操纵局部TGF-β 1水平。 额外的研究来 在猪梗死模型中和体外培养的心脏中进行 成纤维细胞将测试机械变形， 先前存在的基质和TGF-β 1对定义瘢痕结构和功能具有重要意义。 临床上，急性缺血的及时再灌注 心肌梗死可缩小梗死范围，保护左室功能。 这种方法已成为治疗的选择在数小时内冠状动脉 闭塞 有证据表明，强度和胶原蛋白含量 再灌注疤痕不同于永久性闭塞心肌的疤痕。 然而，除了这些观察之外，对疤痕结构知之甚少， 在冠状动脉闭塞的情况下边缘心肌的功能， 再灌注 因此，作为该提案的第三个目标，申请人将 在梗塞-再灌注猪心肌中检查结构特征和 瘢痕组织的机械性能以及在边缘的功能 心肌